1. Technical Field
The present invention relates generally to methods to improve hearing in subjects. More particularly, the present invention relates to the use of novel compositions to promote partial or complete restoration of hearing in a subject.
2. Description of the Related Art
Millions of people are debilitated by hearing loss: almost 49 million people in the US and over 249 million worldwide suffer from hearing impairments (Cotanche and Kaiser, Hear Res. 266(1-2): 18-25 (2010)). The frequency and severity of hearing loss increases with age: 17% of children under age 18, 30% of people over 65, and over 90% of people over 80 have a substantial hearing loss. Id. Although rarely life-threatening, hearing loss affects more people than epilepsy, multiple sclerosis, spinal injury, stroke, Huntington's and Parkinson's diseases combined and has a huge financial impact on our economy and lifestyle (Hudspeth, Neuron. 19: 947-950, (1997)).
Hearing impairment is mainly caused by damage to the cochlear hair cells, the sensory cells in the cochlea. Cochlear hair cell damage can result from a number of causes, including age-related damage or loss (presbycusis), noise exposure, drug exposure, e.g., aminoglycoside antibiotics and anti-cancer therapeutics, infections, syndromic and non-syndromic genetic mutations, and autoimmune disease.
In mammals, loss of cochlear hair cells results in permanent hearing loss because they are generated only during embryonic development and do not regenerate during one's lifetime (Ruben, Acta Otolaryngol Suppl. 220:1-44, (1967)). Avians however, have the ability to regenerate cochlear hair cells throughout their lifetime (Cotanche, Hear Res. 30: 181-196, (1987); Cruz et al., Arch Otolaryngol Head Neck Surg. 113: 1058-1062, (1987); Corwin and Cotanche, Science. 240: 1772-1774, (1988); Ryals and Rubel, Science. 240: 1774-1776, (1988); Lippe et al., Hear Res. 56: 203-210, (1991)). Cochlear hair cell regeneration in avians is not merely a delayed developmental response, as six-year-old quails (which is three years beyond their average lifespan) can regenerate hair cells as readily as newborn chicks (Ryals and Rubel, 1988).
Currently, treatments for hearing loss include electronic cochlear implants, hearing assistive technology, audiologic rehabilitation, and the use of hearing aids. All of these treatment modalities have relatively limited therapeutic potential and more importantly, do not address the problem of restoring cochlear structure and function. However, attempts to restore cochlear structure and function in the mammalian cochlea have been disappointing, at best. In fact, to date, no clinically acceptable treatments exist for regeneration of the human cochlea to treat or prevent hearing loss.
Thus, while cochlear hair cell regeneration offers the promise of a therapeutic treatment for sensorineural hearing loss in humans, this promise is far from being realized. Accordingly, there is a substantial long-felt, but unmet, need in the art for therapeutic compositions and methods that promote mammalian hair cell regeneration. The present invention offers solutions to these and other problems vexing the art.